Table 1.
Summary of Major Phase 2 and 3 Clinical Trials With Bevacizumab in Treatment of Glioblastoma
| Authors, YearRef | Treatment Groups | Type of Trial and Treatment Setting | Number of Patients | Endpoints | P value | Hazard Ratio for Death (95% CI) | Rates of Grade ≥3 Toxicity in BEV group |
|---|---|---|---|---|---|---|---|
| Wick et al, 201711 | CCNU + BEV vs CCNU alone | Phase 3 recurrent | 437 | mPFS (4.2 vs 1.5 months) | <.001 | 0.49 (0.39-0.61) | VTE: 4.9% HTN: 23.7% Hematologic: 53.7% |
| mOS (9.1 vs 8.6 months) | .65 | 0.95 (0.74-1.21) | |||||
| Herrlinger et al, 201616 | RT+BEV, followed by BEV + irinotecan vs RT + TMZ, followed by TMZ | Phase 2 newly diagnosed, MGMT unmethylated | 182 | 6-month PFS (79.3% vs 42.6%) | <.001 | 0.57 (0.41-0.80) | VTE + HTN: 11.8% |
| mOS (16.6 vs 17.5 months) | N/A | 1.02 (0.71-1.48) | |||||
| Taal et al, 201412 | CCNU vs BEV vs CCNU + BEV | Phase 2 recurrent | 153 | Nine-month OS (43%) vs 38% vs 63% | N/A | N/A | HTN: 26% Infection: 6% |
| Gilbert et al, 201410 | TMZ +RT + BEV vs TMZ + RT + placebo | Phase 3 newly diagnosed | 637 | mPFS (10.7 vs 7.3 months) | .007 | 0.79 (0.66-0.94) | HTN: 4.2% VTE: 7.7% Serious bleed: 1.5% |
| mOS (15.7 vs 16.1 months) | .21 | 1.13 (0.93-1.30) | |||||
| Chinot et al, 20149 | TMZ + RT + BEV vs TMZ + RT + placebo | Phase 3 newly diagnosed | 921 | mPFS (10.6 vs 6.2 months) | <.001 | 0.64 (0.55-0.74) | HTN: 11.3% VTE: 7.6% CNS bleed: 2% |
| mOS (16.8 vs 16.7 months) | .1 | 0.88 (0.76-1.02) | |||||
| Narayana et al, 201217 | RT/TMZ + BEV 10 mg/kg | Phase 2 newly diagnosed | 51 | mPFS 13 months mOS 23 months | N/A | N/A | Bleed: 9.8% DVT: 3.9% |
| Lai et al, 201115 | RT/TMZ + BEV 10 mg/kg | Phase 2 newly diagnosed | 70 | mPFS 13.6 months mOS 19.6 months | N/A | N/A | CVA: 9% CNS bleed: 3% HTN: 11% |
| Friedman et al, 200913 | Group 1: BEV | Phase 2 recurrent | 85 | Six-month PFS (42.6%) ORR (28.2%) | N/A | N/A | HTN: 8.3% Convulsion: 6% |
| Group 2: BEV + irinotecan | 82 | Six-month PFS (50.3%) ORR (37.8%) | N/A | N/A | CNS bleed: 1% Convulsion: 13.9% | ||
| Kreisl et al, 200914 | BEV 10 mg/kg + irinotecan | Phase 2 recurrent | 48 | Six-month PFS (29%) 6-month OS (57%) | N/A | N/A | VTE: 12.5% HTN: 12.5% |
| Gutin et al, 200918 | BEV 10 mg/kg + RT | Phase 2 recurrent | 25 | Six-month PFS (65%) mOS 12.5 months | N/A | N/A | CNS bleed: 4% |
| Vredenburgh et al, 20076 | Cohort 1: BEV 10 mg/kg + irinotecan Cohort 2: BEV 15 mg/kg + irinotecan | Phase 2 recurrent | 35 | Six-month PFS (46%) 6-month OS (77%) | N/A | N/A | VTE: 11% CNS bleed: 2% |
Abbreviations: BEV, bevacizumab; CVA, cerebral vascular accident; HTN, hypertension; MGMT, O(6)-methylguanine-DNA methyltransferase; mOS, median overall survival; mPFS, median progression-free survival; ORR, overall response rate; RT, radiation therapy; TMZ, temozolomide; VTE, venous thromboembolism.